Tibet Plateau Medical Research Institute, People's Hospital of Tibet Autonomous Region, Lhasa 850000, China.
Department of Occupational Diseases, The Second Affiliated Hospital of Chengdu Medical College Nuclear Industry 416 Hospital, Chengdu, Sichuan 610051, China.
Eur J Pharm Sci. 2024 Oct 1;201:106857. doi: 10.1016/j.ejps.2024.106857. Epub 2024 Jul 18.
High-altitude polycythemia (HAPC) is a common chronic altitude disease caused by living in low-pressure and low-oxygen environment. At present, there is still no effective cure for HAPC. HIF-2α may play an important role in the development of HAPC in regulating the increased red blood cell excessively induced by HIF-EPO and the blood vessel formation induced by VEGF-VEGFR. Here, we established a rat HAPC model and treated it with the HIF-2α inhibitor PT2385. We mainly evaluated the therapeutic effect of PT2385 on HAPC rats by observing the changes in rat phenotype, tissue and organ damage, red blood cell and hemoglobin content, angiogenesis, lipid peroxidation reaction, and inflammatory factors. The results showed that PT2385 treatment improved the congestion phenotype characteristics, inhibited increased erythrocytes and hemoglobin, reduced blood vessel formation, lipid peroxidation, and inflammation, and reduced tissue and organ damage in HAPC rats. This study preliminarly explains the physiological, pathological, and immunological effects of PT2385 treatment for HAPC. It provides a new idea, a reliable experimental basis, and theoretical support for the clinical prevention and treatment of HAPC.
高原红细胞增多症（HAPC）是一种常见的慢性高原病，由生活在低压低氧环境中引起。目前，HAPC 仍然没有有效的治疗方法。HIF-2α 可能在调节 HIF-EPO 过度诱导的红细胞增加和 VEGF-VEGFR 诱导的血管形成方面在 HAPC 的发展中发挥重要作用。在这里，我们建立了大鼠 HAPC 模型，并使用 HIF-2α 抑制剂 PT2385 进行治疗。我们主要通过观察大鼠表型、组织和器官损伤、红细胞和血红蛋白含量、血管生成、脂质过氧化反应和炎症因子的变化来评估 PT2385 对 HAPC 大鼠的治疗效果。结果表明，PT2385 治疗改善了充血表型特征，抑制了红细胞和血红蛋白的增加，减少了血管形成、脂质过氧化和炎症，减轻了 HAPC 大鼠的组织和器官损伤。这项研究初步解释了 PT2385 治疗 HAPC 的生理、病理和免疫学效应。它为 HAPC 的临床预防和治疗提供了新的思路、可靠的实验依据和理论支持。
